Indian researchers develop nanozymes that can block HIV reactivation
Bengaluru, Apr 1: Researchers at the Indian Institute of Science (IISc) here have developed artificial enzymes that they said can successfully block reactivation and replication of the Human Immunodeficiency Virus (HIV) in the host's immune cells.
Made from vanadium pentoxide nanosheets, these "nanozymes" work by mimicking a natural enzyme called glutathione peroxidase that helps reduce oxidative stress levels in the host's cells, which is required to keep the virus in check, an IISc statement said on Thursday.
The study, published in 'EMBO Molecular Medicine, was led by Amit Singh, Associate Professor and Wellcome Trust-DBT India Alliance Senior Fellow at the Department of Microbiology & Cell Biology and Centre for Infectious Diseases Research (CIDR), and Govindasamy Mugesh, Professor at the Department of Inorganic and Physical Chemistry.
"The advantage is that the nanozymes are stable inside biological systems and do not mediate any unwanted reactions inside the cells," Mugesh said. "They are also quite easy to prepare in the lab."
There is currently no way to eliminate HIV from a patient's body completely, according to the statement.
Anti-HIV drugs are only successful in suppressing the virus; they fail at eradicating HIV from infected cells. The virus hides inside the hosts immune cells in a "latent" state and stably maintains its reservoir.
When the levels of toxic molecules such as hydrogen peroxide increase in the host's cells, leading to a state of increased oxidative stress, the virus gets "reactivated" - it emerges from hiding and begins replicating again, it said.
A few years ago, Amit Singh's team developed a biosensor to measure oxidative stress levels in HIV-infected immune cells in real-time, it was stated.
"We found that to come out of latency and reactivate, HIV needs very little oxidative stress," he said.
One way to prevent reactivation is to keep the oxidative stress constantly low, which would "lock" the virus in a permanent state of latency.
Enzymes such as glutathione peroxidase are essential for this process; they convert toxic hydrogen peroxide to water and oxygen. However, inducing the host cells to produce more quantities of these enzymes could disrupt the tightly regulated cellular redox machinery.
Around the same time, Mugesh's group published a study showing that nanowires made of vanadium pentoxide can efficiently mimic the activity of glutathione peroxidase.
Singh's lab, therefore, decided to collaborate with them.
The researchers prepared ultrathin nanosheets of vanadium pentoxide in the lab and treated HIV-infected cells with them.
The sheets were found to reduce hydrogen peroxide just as effectively as the natural enzyme and prevent the virus from reactivating.
"We found that these nanosheets were having some sort of direct effect where the expression of the host genes essential for virus reactivation is reduced," said Shalini Singh, first author and Research Associate at CIDR.
When the team treated immune cells from HIV-infected patients undergoing antiretroviral therapy (ART) with the nanozymes,latency was induced faster and subsequent reactivation was suppressed when therapy was stopped, indicating that combining the two was more effective, she added.
Combining ART with the nanozymes also has other advantages.
Some ART drugs can cause oxidative stress as a side effect, which can damage heart or kidney cells, Amit Singh said.
"Adding a nanozyme like this can help in reducing the side effects caused by such ART drugs." This can improve the quality of life of HIV patients undergoing treatment.
Although the nanozymes were found to be harmless to normal cells in lab tests, Mugesh said further studies are needed to understand if they can have other effects once they are introduced inside the body.
"Where will they go? Which organs will they enter? How long will they stay in the body? We need to look at all these aspects," he added.
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MP HC sets up judicial commission to probe water contamination in Indore
Indore (PTI): The Indore bench of Madhya Pradesh High Court on Tuesday set up a commission of inquiry comprising a former HC judge to probe the issue of water contamination in city's Bhagirathpura, saying the matter requires probe by an independent, credible authority and "urgent judicial scrutiny".
It also directed the commission to submit an interim report after four weeks from the date of commencement of proceedings.
A division bench of Justices Vijay Kumar Shukla and Alok Awasthi constituted the commission while hearing several public interest litigations (PILs) filed simultaneously regarding the deaths of several people in Bhagirathpura due to the consumption of contaminated water.
The HC reserved the order after hearing all the parties during the day, and released it late at night.
The state government on Tuesday told the HC that the deaths of 16 people in Indore's Bhagirathpura area was possibly linked to a month-long outbreak of vomiting and diarrhoea caused by contaminated drinking water.
The government presented an audit report of 23 deaths from the current gastroenteritis epidemic in Bhagirathpura before the bench, suggesting that 16 of these fatalities may have been linked to the outbreak of vomiting and diarrhoea caused by contaminated drinking water.
The report, prepared by a committee of five experts from the city's Government Mahatma Gandhi Memorial Medical College, stated that the deaths of four people in Bhagirathpura were unrelated to the outbreak, while no conclusion could be reached regarding the cause of death of three other people in the area.
During the hearing, the high court sought to know from the state government the scientific basis behind its report.
The division bench also expressed surprise at the state government's use of the term "verbal autopsy" in relation to the report, sarcastically stating that it had heard the term for the first time.
The HC expressed concern over the Bhagirathpura case, stating that the situation was "alarming," and noted that cases of people falling ill due to contaminated drinking water have also been reported in Mhow, near Indore.
In its order, the HC said the serious issue concerning contamination of the drinking water supply in Bhagirathpura area allegedly resulted in widespread health hazards to residents, including children and elderly persons.
According to the petitioners and media reports, death toll is about 30 till today, but the report depicts only 16 without any basis or record, it said.
It is averred that sewage mixing, leakage in the pipeline, and failure of civic authorities to maintain potable water standards have led to the outbreak of water-borne diseases. Photographs, medical reports, and complaints submitted to the authorities prima facie indicate a matter requiring urgent judicial scrutiny, the HC said.
"Considering the gravity of the allegation and affecting the right to life under Article 21 of the Constitution of India and the need for an independent fact-finding exercise, the Court is of the opinion that the matter requires investigation by an independent, credible authority," it said.
"Accordingly, we appoint Justice Sushil Kumar Gupta, former judge of the Madhya Pradesh High Court, a one-man commission of inquiry into the issues relating to water contamination in Bhagirathpura, Indore, and its impact on other areas of the city," the HC added.
As per the order, the commission shall inquire into and submit a report on the cause of contamination -- whether the drinking water supplied to Bhagirathpura was contaminated; and the source and nature of contamination (sewage ingress, industrial discharge, pipeline damage etc).
The panel will also probe the number of actual deaths of affected residents on account of contaminated water; find out the nature of disease reported and adequacy of medical response and preventive measures; suggest immediate steps required to ensure safe drinking water as well as long-term infrastructural and monitoring reforms.
It will also identify and fix responsibility upon the officers and officials found prima facie responsible for the Bhagirathpura water contamination incident, and suggest guidelines for compensation to affected residents, particularly vulnerable sections.
The commission shall have powers of a civil court for the purpose of summoning officials and witnesses; calling up records from the government department, hospitals, laboratories and civic bodies; ordering water quality testing through accredited laboratories; conducting spot inspections.
All state authorities involving district administration, Indore Municipal Corporation, public health engineering department and Madhya Pradesh Pollution Control Board shall extend full co-operation and provide records as sought by the commission, it said.
The state government shall provide office space, staff, and logistical support to the commission, it said.
During the hearing in the day, the state government also presented a status report to the court in this matter.
According to reports, a total of 454 patients were admitted to local hospitals during the vomiting and diarrhea outbreak, of whom 441 have been discharged after treatment, and 11 are currently hospitalised.
According to officials, due to a leak in the municipal drinking water pipeline in Bhagirathpura, sewage from a toilet was also mixed in the water.
